A process for producing substituted vinyl pyridines having inhibitory activity against TXA.sub.2 synthetase has been already known (Japanese Patent Laid Open Publication No. 219162/1983). However, when this process is studied in detail, the production conditions have various problems from the viewpoint of safety and particularly, in the case of expansion of the production scale, there may be a danger that a serious accident would happen.
That is, in Japanese Patent Laid Open Publication No. 219162/1983, in order to produce a substituted vinyl pyrdine compound of the general formula: ##STR3## wherein R.sup.1' is pyridyl group; R.sup.2' is phenyl group optionally having a lower alkoxy group, a lower alkyl group, a halogen atom, trifluoromethyl group, a lower alkenyl group or methylenedioxy group, thienyl group, furyl group, naphthyl group, benzothienyl group or pyridyl group; Y is methylene group; R.sup.3' is hydrogen atom or a lower alkyl group; and n' is an integer of 0 to 6, a compound of the general formula: ##STR4## wherein R.sup.1' and R.sup.2' are as defined above, is reacted with a compound of the general formula: EQU (C.sub.6 H.sub.5).sub.3 P.sup.+ --CH.sub.2 CH.sub.2 CH.sub.2 --CH.sub.2).sub.n' COOR.sup.3'.X.sup.- (III)
wherein X is a halogen atom; and R.sup.3' and n are as defined above, in a solvent in the presence of a base. It is disclosed that, as this base, there can be used n-butyl lithium, sodium hydride, potassium tertiary butoxide and the like and, among them, n-butyl lithium and sodium hydride are preferred. As the solvent, for example, ether, tetrahydrofuran, dimethylformamide, dimethylsulfoxide or a mixed solvent of two or more of these solvents is disclosed There are disclosed that this reaction is preferably carried out under the atmosphere of a dried inert gas (e.g., nitrogen gas, helium gas or the like), and that the reaction temperature is -10.degree. C. to 50.degree. C., preferably 0.degree. C. to 30.degree. C., and the progress of the reaction can be monitored by observing disappearance of the characteristic color of phospholane, and the reaction is normally completed within about 1 to 6 hours.
In this process, with regard to most of combinations of these solvents and bases, danger has been hitherto pointed out and accidents such as explosion and the like have been reported. Examples of these accidents were as follows: (1) It has been reported that, when sodium hydride or an alkoxide such as sodium methoxide or the like was used in dimethylformamide, dimethylformamide was exothermically decomposed to produce carbon monoxide as a by-product, which induced runaway reaction ["Chemistry and Industry", 17, Feb., 1984, 134; "Chem. Eng. News", 1982, 60 (28), 5; "Chem. Eng. News", 1982, 60, Jul., 12, 5; and "Chem. Eng. News", 60, September 13, 5]; (2) It has been reported that, when the reaction was carried out by using sodium hydride in dimethylsulfoxide, dimethylsulfinyl anion was produced, which caused explosion ["Chem. Eng. News", 1966, 44, April 11, 48; and "Chem. Eng. News", 1966, 44, June 13, 7]; and (3) It has been reported that, when a hydride was refluxed in tetrahydrofuran, explosion was caused (this has been reported with regard to calcium hydride) ["Chem. Eng. News", 1987, 56, February 6, 3; and "Chem. Eng. News", 1987, April 17, 68]. Further, to use a large amount of a hydride which generates hydrogen in a solvent having a low flash point such as ethyl ether or the like is accompanied with the same danger as those described above, and n-butyl lithium is extremely sensitive to moisture, which renders its handling disadvantageous.